This proposal is to request support for a Keystone Symposia meeting entitled "Overcoming TB and AIDS", organized by Anne E. Goldfeld and Stefan H.E. Kaufmann, which will be held in Arusha, Tanzania from October 21 - 25, 2009. Tuberculosis (TB) is the largest cause of death in the AIDS setting, having caused approximately 50% of all AIDS deaths globally. Each infection on its own manipulates the host immune response to enhance the other infection's pathogenicity, and the treatment of each involves long or lifelong therapy of complicated drug regimens. The focus of this Keystone Symposia meeting is to gain deeper insights into the immune pathology and deadly synergism between HIV and TB and its global toll in order to identify new ways to solve this global catastrophe by way of basic scientific discovery, and the development and delivery of vaccines, drugs and care. Mycobacterium tuberculosis survives in the vast majority of infected individuals without causing disease. However, as HIV compromises the immune system it fuels clinical emergence of TB and, as a result, has become the driving force for the current TB epidemics in Subsaharan Africa and Asia. TB in turn drives HIV-1 replication and causes HIV-1 disease progression. In order to effectively tackle this twin epidemic, integrated approaches encompassing basic immunological research, drug discovery, drug and vaccine design and delivery and novel approaches to delivering care in remote and impoverished areas must be integrated. This includes the following: virologic and bacteriologic research on the pathogens themselves;immunologic, molecular and cellular research on the host response;design, development and delivery of drugs and vaccines;development of different technologies for biomarkers of disease and cure;and novel drug and vaccine delivery systems. Moreover, basic discovery must be synergized with novel approaches to the delivery of TB and AIDS care in endemic areas. The overarching goal of the symposium is to gain a broad perspective on the problem of TB/AIDS - from its impact on life on earth to the basic biology of the organisms, the immune response - and to develop new paradigms of thinking and responses to deal with the humanitarian catastrophe of TB and AIDS co-infection.